ME-foreldrene blog: Lecture by Hanne Thürmer, Notodden. RituxME and current development, 13 April 2016
Lecture by dr Hanne Thürmer, Notodden Hospital Original in Norwegian/Norsk original
From a lecture given at the local department of the Norwegian ME-association in Notodden, avd Telemark, Norway, February 8th 2016.
Lecturer: Hanne Thürmer, dr. med at Notodden Hospital.
Dr Hanne Thürmer is a senior consultant in the field of internal medicine and cardiovascular diseases, and has been involved in ME since 2009. She is also a member of the Norwegian ME-association’s Board of Medicine. Here are our notes from the lecture.
The slides from this evening in Norwegian: sykdomslære ME jan 2016
Ann Kristin Bakken of the ME-association in Notodden welcomed everybody to this evening at LMS Notodden Hospital.
ME/CFS/SEID Status 2016
This illness has several names. SEID might be the most accurate this far. It originates from the USAs National Institute of Medicine. [See their report from 2015]
Notodden Hospital has had a clinic for ME-patients since 2009.
In Notodden it all started with a young and very sick patient whom the doctors at the hospital tried to help. The doctors got curious and tried to learn more. This way they increased their knowledge about ME and Notodden became one of the larger Norwegian clinics. At Notodden we use the Canadian Criteria and the International Consensus Criteria.
Notodden has had approx 400 patients since 2009 [Norwegian].
Patients are mostly female (80 %).
They have a small increased tendency to get a rare disease called B-cell lymphoma. The doctors think the B-lymphocytes are important.
The doctors notice that there is a tendency that ME-patients have more autoimmune diseases like coeliac disease, arthritis etc. POTS is quite common, the patients have body systems that are not under control. Symptoms for POTS are, among others, a drop in blood pressure and rapid pulse. This is a symptom of the body not being able to regulate itself, not the cause of ME.
The patients are often sensitive to alcohol and their reactions to medications are not normal.
We still do not have well established knowledge about this disease, but a there is a lot developing now. We have a rush of new data and new theories, a lot is tried and discarded underway. It is very difficult to be a patient – and it is not too easy being the doctor either.
Fatigue is the symptom best known.
Fatigue gives the patients reduced ability to start and/or maintain an activity. A lot of patients start doing something that they are not able to finish. The patients find it difficult to concentrate and to keep up their attention level. Their cognitive function is reduced.
Fatigue is not visible and not measureable. Fatigue is not the same as sleepiness, decondition, depression and so forth.
ME/CFS is a lot more than just fatigue.
«In meeting the patients, we try to grasp just how exhausted they are, but it is really difficult because most often they are too exhausted to even remember themselves! », Thürmer says.
The illness is real, it is somatic, it is recognisable, and it can be separated from other conditions. A probable cause is not established, and reliable tests do not exist, yet. As of today, the diagnose is based on criteria and we have to rule out any other disease. We have 20 different sets of criteria, and some of them are almost the same!
SEID might be able to connect the different sets of criteria. New knowledge might give us better tools for diagnosis. We can still examine effects of treatments even though the cause of the disease is still not discovered.
Unfortunately, not all doctors and caseworkers are updated.
It is easier to relate to something visible, and meeting unknown conditions can be challenging – the professional caseworker might become unsecure and unprofessional?
These are common human reactions – to think that this cannot exist, this is exaggerated, this is somebody else’s problem, somebody else has to deal with this. And this in turn makes the patients feel rejected.
NB! Important advice to ME-patients: Never go to meetings alone!
The name
Mostly, the different names of this illness are descriptive. The name Myalgic Encephalomyelitis was launched by the Lancet in 1956, CFS (another descriptive name – chronic fatigue syndrome) came later. The illness has been called neurasthenia and soldiers heart. We are quite certain that Charles Darwin and Florence Nightingale suffered from ME, reading contemporary descriptions.
ME can be epidemic.
SEID is the most recent name, Systemic Exertion Intolerance Disease.
Again, this is a descriptive name. Unfortunately, it is a bit difficult to translate to Norwegian. The concept of the disease being systemic is very important!
How many people suffer from ME?
The numbers are unsure but we operate with around 1–2 per 1000 people, which means 170–340 new cases per year here in Telemark [county].
ME is graded in four categories of severity
1: mild, self manageable, needs to rest. Not well and healthy.
Memory-problems occur already at this mild level.
2: moderate, needs to rest every day
3: severe, big memory-problems, mostly resting. Housebound.
4: very severe, dark room and so forth. This is rare, fortunately.
The symptoms are diverse
We see cognitive impairment – memory, concentration, attention. Of the patients who participate in the RituxME-study and come regularly to our clinic, we always have several patients coming at the wrong time, forgetting their appointment. It happens so often; the staff has routines to handle this.
The patients have a physical malfunction like weakness, exhaustion and they are easily worn out.
They also have a neurological failure
– other: sleep issues, uneven body temperature.
The patients are asked to grade their symptoms on a scale from 1-10, and quite a large number scores high.
What do we agree on?
We have some kind of disposition, and then something happens that sets it off. The illness changes both the immune system and other organs.
The patients experience that they get worse both by physical and psychological strain.
Exercise makes almost all the patients worse. ME is not a psychiatric diagnosis, but psychological reactions can make the illness worse.
A lot of people try to rest the illness away, but total bed rest for long periods does not help them to improve either.
There might be a heritable/genetic vulnerability to ME, but most patients are the single one in their Family.
Criteria for diagnosis
The diagnosis is made by one of the sets of criteria. Here at Notodden Hospital, we use the Canadian criteria, we have a fairly homogeneous group of patients. All other possibilities of illness must be ruled out. Often it takes a long time to be diagnosed, as we still lack an accurate test for ME.
Diagnosis can be made by your GP [children need a specialist], but before applying to benefits the welfare system in Norway (Nav) often require that the patient see a specialist.
Query: «Is there a tendency of over-diagnosis by the GPs? » – We do not know this, it is hard to say. It is not a good thing if all tired patients get a diagnosis of ME …
Illnesses that need to be ruled out before the patient can get diagnosed with ME are infections, immune diseases, it is important to check the metabolism, cancer and other serious illnesses, celiac disease, deficiency diseases, abuse of pills and other narcotics, depression etc.
Hallmarks
The patient has previously functioned just fine in everyday life, with a job, and recreational activities – more often than not plus a little extra activity in the community. Then something happens to some, maybe an infection? Then we see an after-condition that we do not understand, that lasts for year after year. The patient is not able to restart, exercise leads to relapse, the doctors mistrust the patient, the welfare system mistrusts the patient, and this is frustrating and depressing.
Cognitive therapy does help in somatic disease – we use the technique in all other groups of patients to help them rid themselves of feelings like guilt, low self esteem, it is important to build confidence and pride to get a little bit better.
More on treatment
Long cures of antibiotics have been tried out, but on average, it doesn’t help. There are disadvantages to using antibiotics for long periods of time so one has to be careful. Long cures are to be avoided. EryMax (antibiotic) and macrolides can be helpful –in the short run. In this case it is not the antibiotic itself that is helpful, but another function (nitrogen).
Patients need to be careful; there are a lot of people who want to make a profit on all kinds of tests and cures that are not reliable.
Some make a lot of money on these tests and we cannot see that this is useful for the patients, but we do understand that some patients are desperate and willing to try everything.
There has not been found fungus, virus or bacteria in the bodies of ME patients.
On the other hand the function of the B-lymphocytes is a possible contributing factor (this is a theory). B-lymphocytes are a type of white blood cells and they are a part of the immune system.
FODMAP elements in diet can make the patient worse. Irritable Bowel Syndrome (IBS) is the ME of the bowel and is often found in the same patients.
LDN helps some; one can try out starting at 3 mg then increase, stop and start again (some patients improved so much on LDN that they didn’t want to participate in RituxME). This treatment is not documented. It looks like it is mostly helpful if the patient has a lot of pain issues.
Vitamin supplements. B12, D-vitamins. Some, as in the Marshall Protocol, say that one should run the levels all the way down! It is better to have an appropriate level of vitamins and minerals.
Nitroglycerin can be of help, we are testing this in the study of the endothelial function on a blood vessel in the patient’s arm. It helps some patients while it gives other patients a headache. This is something that can be tested, and it is not expensive! It is a spray under the patient’s tongue. In some patients the effect lasts for 3 days! Usually, the effect passes within a few minutes, but the body of ME-patients do not react normally. It is not dangerous to try out nitroglycerin.
Gammanorm, supplement of immunoglobulin: we need a serious study of this. Some find that it is helpful, while others get worse.
Gammanorm-treatment has somewhat of the opposite effect of what the Rituximab-study is testing.
(The reason for this might possibly be that there is an imbalance in the immune system and maybe several types of ME. Maybe some patients produce too much immunoglobulin, while others produce too little? We cannot predict this yet, but we might know a little more by the fall of 2017. Some patients get every disease that goes around, and some get nothing. This indicates at least two types of ME. In any case this certainly has something to do with the immune system.)
Rituximab and cyclophosphamide are immunosuppressants or immune modulating agents. There are ongoing studies on the effect on ME-patients in Bergen (Haukeland hospital) and in several other hospitals in Norway.
Scientific basis for today’s treatment
It is important to avoid crashing; the patient needs to be stabilized before he or she can get better. The head needs to be in charge of the level of activity. One does not get well this way, but one can get a bit better. Stabilize on 70 % of available energy. [Do not use more than 70% of the energy available (editor)]
Query: «Where does the extra energy come from? » – The patients often have a strong will. You just don’t back down.
Query: «But is it adrenaline? Cortisol? » – Everything is different and more undulating in patients with ME, it is difficult to measure but it does vary in healthy persons as well.
Perpetuating factors can be outer and inner stress, too much activity, diet, too little relaxation …
It is important to stop all treatment that is not working. It might be antibiotics, hair-testing, expensive supplements, total bedrest, and exercising without customization…
ME-patients must be in control, live controlled, the frame is limited.
The patients need to adjust according to their level of functioning.
There is a big individual difference in how much activity that is tolerated. One method can be to keep track of reactions 2–3 days after any kind of activity and then evaluate if this was on the right level. It is very important to stay within the limits.
How do the children progress?
We are not as positive as we used to be. These are figures from Dr.
Bell in Lyndonville, 25 years after disease onset: 40 % of patients are ok, 40 % are quite good and 20 % remain ill.
Those who are very poor or have been sick more than 5 years rarely recover fully. Recovery is rarer the worse the child has been and the longer the child has been sick.
[Added from the slide:] They need to live highly regulated and “level”, and adapt school, family and socializing to M.E. all the time.
How do the adults progress?
Almost no adults recover completely, one must stabilize. Most are not able to get back to regular 100 % jobs and have a normal everyday life. Patients can live a little better if they are careful not to “crash”. We see that courses, initiatives and activities beyond their abilities (for example those imposed by the Norwegian welfare office
(Nav)) make them worse. Bad conscience makes patients worse, that’s no wonder.
Query: «Does the disease affect age deterioration?» – We do not know, but life expectancy are not shorter among people with ME.
Function level
To figure out the level of functioning, we can ask questions like – Do you have to choose between taking a shower and having breakfast? etc.
We use these questions not to miss what the actual functional level of the patient is. The level of functioning is usually very low! Many patients forget how sick they really are. It’s awkward for the patients to be reminded of how ill they are. One of the most common coping strategies is to forget how sick you are! This is one of the reasons why you NEVER should go alone to meetings, for example to The welfare office (Nav). Take someone with you, do not say yes to anything you know will go wrong. You must complain, and complain again if they make wrong decisions. You can get help from the ME-Association or a lawyer. Get help to file a complaint. The problem is that Nav have no alternative to “working trials”. The Nav in the county of Telemark will soon attend a course on ME.
We have tried to measure the ME patients’ fatigue with a bicycle exercise test for two consecutive days, where we monitor the level of lactic acid, which turns out to be disturbed. The problem is that the test is too hard on the patients, it is obvious that there is something wrong with them. Patients are bedridden for months afterwards, so the test cannot be used on the more severe cases.
One theory we are testing is whether the endothelial organ may be damaged:
We measure the blood vessel in the arm, using a blood pressure monitor and look at the expansion of the blood vessels in patients.
Nitroglycerin allows the blood vessels to react normally.
This is a promising test, but not unambiguous, either. In some patients it is very obvious and unusual.
In a few years now we are sure to get good tests!
The RituxME study 2015-2017
The story is getting well known. It started with a woman with lymphoma and ME who got much better from her ME when she received treatment for her cancer. This made the Haukeland doctors start testing.
In the first studies 70 % of the patients improved, while 30 % had no changes. These are small studies and few patients.
In the patients who improved, EVERYTHING got better! Not just one symptom, but the whole package. People felt completely healthy. The questions the doctors then asked themselves was: What is happening?
Why did 1/3 have no effect? Could there be subtypes that have something to do with the immune system?
Notodden Hospital is one of the centers where research on Rituximab is carried out [Norwegian].
Rituximab and the RituxME study
Rituximab is a medicine that has been used for a long time on other groups of patients.
In the study intravenous infusion is used.
Rituximab kills all B-lymphocytes, and it takes 3-7 months before symptoms improve. Some patients have years of effect, while some have a relapse after the B-lymphocytes come back.
The pharmaceutical company is working on developing a syringe that can be set in the stomach skin, as some patients presumably must take this medication regularly, throughout life, such as diabetics must take insulin. It already exists as such a syringe for other patients with other diseases.
Presently some of the 32 participants at Notodden [Thürmers hospital] have become much better, but we do not know if they belong to the placebo group or if they receive medicine. We will not know until 2017.
The RituxME study takes place at 5 centers in Norway, and at Notodden we have patients from Risør to Drammen. A total of 152 patients in Norway are included in the study.
The drug has been used for 20 years, but we must find out whether it is safe for this patient group. It destroys the immune system.
Query: «Are there serious side effects?» – MabThera (which is the same as Rituximab) has been used for many years. It’s about the same mortality rate as paracetamol.
Cyclophosphamide is stronger, but it does not give as many side effects and can be given to the most severely affected. (It is being researched in another study at Haukeland, not in Notodden.)
Query: «How will the approval procedure be if Rituximab proves to be effective?» – It’s depends a bit on how clear the effect is. If there still are 70 % who improve, the approval may go quickly. This is easier than if it [the drug] were something completely new.
Query: «What about Rituximab for children?» – Children will have to wait longer, it’s safer for adults. We do not know enough to give clear answers. But we are generally more careful with children because of growth and vulnerability.
Assessment
The GP should be able to provide diagnosis. The physician must be a specialist in general practice. Then it should be okay. Your physician may use a tool for assessment that for instance the one that Notodden Hospital can send out. This is a standard ME-assessment package. We can even send it out via the ME Association also, if desired.
Advice for the future
To get a better life, it makes sense not to wait for miracle cures, they get here when they get here. Try to have some social life, try dieting. Set realistic goals. Note that the classical method of exercise makes you worse and that the right amount of activity for an ME patient is very little!
We at Notodden Hospital train the Nav in the county of Telemark. This does not happen many places, but here in Telemark they are very interested. There is great need for this in Nav, as the caseworkers are very unsecure.
Query: «Is there any connection or resemblance between ME and fibromyalgia? Many have both diagnoses.» – There is a 70 % overlap between ME and fibromyalgia; we think it is impossible to prove whether there are two diseases or just one.
Presumably the ME gives fibromyalgia-like symptoms and then the patient gets both diagnoses.
Remember that what I say today is certainly not right in six months time, and definitely not in 10 years!
Thank you for attending.
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This report and translation is published in agreement with Dr. Hanne Thürmer, but the referent takes full responsibility for any wrong citation and misunderstanding.
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